NM_000156.6(GAMT):c.414_415del (p.Ser140fs) AND Cerebral creatine deficiency syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 23, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001390318.7

Allele description [Variation Report for NM_000156.6(GAMT):c.414_415del (p.Ser140fs)]

NM_000156.6(GAMT):c.414_415del (p.Ser140fs)

Gene:

GAMT:guanidinoacetate N-methyltransferase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000156.6(GAMT):c.414_415del (p.Ser140fs)

HGVS:

NC_000019.10:g.1399173_1399174del
NG_009785.1:g.7381_7382del
NM_000156.6:c.414_415delMANE SELECT
NM_138924.3:c.414_415del
NP_000147.1:p.Ser140fs
NP_620279.1:p.Ser140fs
NC_000019.9:g.1399171_1399172del
NC_000019.9:g.1399172_1399173del

Protein change:

S140fs

Links:

dbSNP: rs2144636856

NCBI 1000 Genomes Browser:

rs2144636856

Molecular consequence:

NM_000156.6:c.414_415del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_138924.3:c.414_415del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cerebral creatine deficiency syndrome (CCAD)
Synonyms:: Creatine deficiency syndromes
Identifiers:: MONDO: MONDO:0000456; MedGen: C5244016; Orphanet: 79172; OMIM: PS300352

Recent activity

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ecotropic viral integration site 2B [Homo sapiens]
ecotropic viral integration site 2B [Homo sapiens]
gi|20070235|ref|NP_006486.2|

Protein
RecName: Full=Epithelial discoidin domain-containing receptor 1; Short=Epithelia...
RecName: Full=Epithelial discoidin domain-containing receptor 1; Short=Epithelial discoidin domain receptor 1; AltName: Full=CD167 antigen-like family member A; AltName: Full=Cell adhesion kinase; AltName: Full=Discoidin receptor tyrosine kinase; AltName: Full=HGK2; AltName: Full=Mammary carcinoma kinase 10; Short=MCK-10; AltName: Full=Protein-tyrosine kinase 3A; AltName: Full=Protein-tyrosine kinase RTK-6; AltName: Full=TRK E; AltName: Full=Tyrosine kinase DDR; AltName: Full=Tyrosine-protein kinase CAK; AltName: CD_antigen=CD167a; Flags: Precursor
gi|729008|sp|Q08345.1|DDR1_HUMAN

Protein
Nucleotide Links for Protein (Select 1917203475) (9)
Nucleotide
Conserved Domain Links for Protein (Select 1917203475) (2)
Conserved Domains

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001592002	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001592002

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 23, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001592002.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change results in a premature translational stop signal in the GAMT gene (p.Ser140Glyfs*50). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 97 amino acids of the GAMT protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GAMT-related conditions. This variant disrupts the C-terminus of the GAMT protein. Other variant(s) that disrupt this region (p.Glu176*) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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